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疫苗组学方法用于鉴定控制蜱媒侵袭和感染的候选保护性抗原

Vaccinomics Approach to the Identification of Candidate Protective Antigens for the Control of Tick Vector Infestations and Infection.

作者信息

Contreras Marinela, Alberdi Pilar, Fernández De Mera Isabel G, Krull Christoph, Nijhof Ard, Villar Margarita, De La Fuente José

机构信息

SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCMCiudad Real, Spain.

Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität BerlinBerlin, Germany.

出版信息

Front Cell Infect Microbiol. 2017 Aug 9;7:360. doi: 10.3389/fcimb.2017.00360. eCollection 2017.

Abstract

is an emerging tick-borne pathogen causing human granulocytic anaplasmosis (HGA), tick-borne fever (TBF) in small ruminants, and other forms of anaplasmosis in different domestic and wild animals. The main vectors of this pathogen are tick species, particularly in the United States and in Europe. One of the main limitations for the development of effective vaccines for the prevention and control of infection and transmission is the identification of effective tick protective antigens. The objective of this study was to apply a vaccinomics approach to - interactions for the identification and characterization of candidate tick protective antigens for the control of vector infestations and infection. The vaccinomics pipeline included the use of quantitative transcriptomics and proteomics data from uninfected and -infected ticks for the selection of candidate protective antigens based on the variation in tick mRNA and protein levels in response to infection, their putative biological function, and the effect of antibodies against these proteins on tick cell apoptosis and pathogen infection. The characterization of selected candidate tick protective antigens included the identification and characterization of homologs, functional characterization by different methodologies including RNA interference, immunofluorescence, gene expression profiling, and artificial tick feeding on rabbit antibodies against the recombinant antigens to select the candidates for vaccination trials. The vaccinomics pipeline developed in this study resulted in the identification of two candidate tick protective antigens that could be selected for future vaccination trials. The results showed that lipocalin (ISCW005600) and lectin pathway inhibitor (AAY66632) and homologs constitute candidate protective antigens for the control of vector infestations and infection. Both antigens are involved in the tick evasion of host defense response and pathogen infection and transmission, but targeting different immune response pathways. The vaccinomics pipeline proposed here could be used to continue the identification and characterization of candidate tick protective antigens for the development of effective vaccines for the prevention and control of HGA, TBF, and other forms of anaplasmosis caused by .

摘要

是一种新出现的蜱传病原体,可引起人类粒细胞无形体病(HGA)、小反刍兽的蜱传发热(TBF)以及不同家畜和野生动物的其他无形体病形式。该病原体的主要传播媒介是蜱种,尤其是在美国和欧洲。开发有效疫苗以预防和控制感染及传播的主要限制之一是确定有效的蜱保护性抗原。本研究的目的是应用疫苗组学方法研究蜱与[病原体名称]的相互作用,以鉴定和表征用于控制蜱侵袭和[病原体名称]感染的候选蜱保护性抗原。疫苗组学流程包括使用来自未感染和[病原体名称]感染蜱的定量转录组学和蛋白质组学数据,根据蜱mRNA和蛋白质水平对感染的反应变化、其假定的生物学功能以及针对这些蛋白质的抗体对蜱细胞凋亡和病原体感染的影响来选择候选保护性抗原。所选候选蜱保护性抗原的表征包括鉴定和表征[病原体名称]同源物,通过不同方法进行功能表征,包括RNA干扰、免疫荧光、基因表达谱分析,以及用针对重组抗原的兔抗体进行人工蜱喂养,以选择用于疫苗试验的候选物。本研究中开发的疫苗组学流程导致鉴定出两种可用于未来疫苗试验的候选蜱保护性抗原。结果表明,脂质运载蛋白(ISCW005600)和凝集素途径抑制剂(AAY66632)及其[病原体名称]同源物构成用于控制蜱侵袭和[病原体名称]感染的候选保护性抗原。这两种抗原都参与蜱逃避宿主防御反应以及病原体感染和传播,但针对不同的免疫反应途径。这里提出的疫苗组学流程可用于继续鉴定和表征候选蜱保护性抗原,以开发用于预防和控制HGA、TBF以及由[病原体名称]引起的其他无形体病形式的有效疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3f/5552662/d5861d693fea/fcimb-07-00360-g0001.jpg

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